EP0527562A2 - Chromatographische Kolonne und Kolonnen-Analysesystem - Google Patents

Chromatographische Kolonne und Kolonnen-Analysesystem Download PDF

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Publication number
EP0527562A2
EP0527562A2 EP92306568A EP92306568A EP0527562A2 EP 0527562 A2 EP0527562 A2 EP 0527562A2 EP 92306568 A EP92306568 A EP 92306568A EP 92306568 A EP92306568 A EP 92306568A EP 0527562 A2 EP0527562 A2 EP 0527562A2
Authority
EP
European Patent Office
Prior art keywords
column
rack
tip portion
eluate
pressure cylinder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP92306568A
Other languages
English (en)
French (fr)
Other versions
EP0527562A3 (en
Inventor
James R. M. Sanford
Patrick M. Frank
Joseph H. Golias
William C. Jennings
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Helena Laboratories Corp
Original Assignee
Helena Laboratories Corp
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Filing date
Publication date
Application filed by Helena Laboratories Corp filed Critical Helena Laboratories Corp
Publication of EP0527562A2 publication Critical patent/EP0527562A2/de
Publication of EP0527562A3 publication Critical patent/EP0527562A3/en
Withdrawn legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/405—Concentrating samples by adsorption or absorption
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8804—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 automated systems
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    • G01N30/02—Column chromatography
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    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G—PHYSICS
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    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G01N2030/8822—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving blood
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    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00524—Mixing by agitating sample carrier
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    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0403—Sample carriers with closing or sealing means
    • G01N2035/0405—Sample carriers with closing or sealing means manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
    • G—PHYSICS
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0429—Sample carriers adapted for special purposes
    • G—PHYSICS
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    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1053—General features of the devices using the transfer device for another function for separating part of the liquid, e.g. filters, extraction phase
    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1067—Multiple transfer devices for transfer to or from containers having different spacing
    • G01N2035/1069—Multiple transfer devices for transfer to or from containers having different spacing by adjusting the spacing between multiple probes of a single transferring head
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/24—Automatic injection systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/38—Flow patterns
    • G01N30/46—Flow patterns using more than one column
    • G01N30/466—Flow patterns using more than one column with separation columns in parallel
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6047—Construction of the column with supporting means; Holders
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/80—Fraction collectors
    • G01N30/82—Automatic means therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/026—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having blocks or racks of reaction cells or cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1067—Multiple transfer devices for transfer to or from containers having different spacing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1081—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
    • G01N35/109—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane with two horizontal degrees of freedom
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/809—Multifield plates or multicontainer arrays

Definitions

  • This invention relates to column chromatography and, more particularly, to an improved column analyzer system which provides for automatic column chromatography and automatic optical density processing. It specifically concerns methods of conducting column chromatography and chromatographic columns per se.
  • the eluate solutions are collected in a series of cuvettes, one cuvette for each eluate solution or fraction. Thereafter, the cuvettes are sequentially processed in an optical reader.
  • This technique is time consuming, permits errors in identification of the cuvettes and exposes the technician handling the cuvettes to biological hazards such as HIV virus which may be carried in the blood specimens.
  • the equipment which automates the processing of columns has heretofore discharged the eluates into a series of test tubes, and then the technician or operator of the equipment had manually to transfer the test tubes to a reader.
  • the present invention aims to overcome or to at least alleviate the shortcomings of the prior art by providing a new and improved column analyzer system and method.
  • the column analyzer system of the present invention seeks to provide for the automated processing of an array of chromatographic columns, including the rupturing of foil seal members from the columns using pressure tip units with seal-punching heads and the removal of caps from the columns using spring members which are deflected by bearing edges provided by the racks in which the columns are mounted, without technician intervention solutions.
  • the present invention further seeks to provide for automatically shaking loose the last drop of eluate from a column to avoid transferring it to the wrong receptacle.
  • the present invention further seeks to provide for an improved chromatography column whose top end is sealed by a foil member.
  • a method of conducting column chromatography comprising the steps of:
  • a third aspect of the present invention there is provided a method of conducting column chromatography, comprising the steps of:
  • a chromatographic column comprising: a hollow plastic shell having a reservoir portion with an end, a tip portion with an end, and a barrel portion connected between the reservoir and tip portions; a chromatographic medium in the barrel portion; and a foil member attached to the end of the reservoir portion to close it, the foil member having a metal layer and at least one plastics layer which separates the metal layer from the shell.
  • Figure 1 illustrates a chromatographic column 10 which includes an upper end or cover 12 threadingly engaged onto the body portion of the column.
  • the body portion of the column includes a downwardly and inwardly tapering reservoir portion 14 communicating with a barrel portion 16, which barrel portion contains a chromatographic medium, such as affinity resin particles, cellulose, ion exchange resin particles, etc.
  • the lower end of the barrel portion 16 tapers downwardly to a tip portion 18 which is covered by a removable cap 20.
  • the column 10 as described and illustrated, including a threadable cover 12 (threads 13 are shown in Figure 4), is conventional.
  • the present invention provides an improved cuvette means 24 which provides for the collection of all of the eluates from a single column within separate cells of a single cuvette means.
  • the cuvette means 24 is a generally rectangular container having opposed, parallel, spaced-apart side walls 26, 28, and opposed, spaced-apart parallel end walls 30, 32 oriented perpendicular to the side walls.
  • the side walls and end walls of the cuvette means are mounted on a base 34, and the side walls and end walls, together with the base, define a rectangular container which is open at the top and closed at the bottom.
  • the cuvette means may include four separate cells. Three interior walls 36a, b, c extend between the side walls 26, 28, with the interior walls being generally parallel to the end walls 30, 32.
  • the cuvette means thus defines four discrete cells 38 a, b, c, d, respectively.
  • Each cell is defined by the base 34, the side walls 26, 28, and two additional walls.
  • the two additional walls are walls 30 and 36a; for cell 38b, the two additional walls are walls 36a and 36b.
  • the two additional walls which define cell 38c are interior walls 36b and 36c.
  • the two additional walls which define cell 38d are walls 36c and 32. It should be noted that cells 38 a, b, c are of generally equal size and are substantially smaller than cell 38d for reasons which will be hereinafter explained.
  • a rack 42 is provided for supporting an array of columns.
  • the rack includes upper and lower plates 44, 46, respectively, supported and maintained in spaced-apart relationship by a plurality of cylindrical rods 48.
  • the upper and lower plates support 50 columns 10 in a 5 x 10 array.
  • the upper plate 44 is provided with a series of circular apertures 50 of a size and shape to receive the barrel 16 of the column 10. Adjacent each circular aperture is a rectangular aperture 52 to accommodate the automatic column cap removal means which will hereafter be explained and to provide access to the cuvettes beneath rack 42.
  • the lower plate 46 includes a plurality of apertures 54 which are generally rectangular in configuration.
  • Each generally rectangular aperture 54 includes opposed short walls, a first longer wall interconnecting the short walls, and a second wall 58 opposed form the longitudinal wall 56, which second wall includes a cutout portion that is generally configured as three-quarters of a circle. The diameter of the cutout portion is configured to support the lower end of the barrel 16 of the column, and is aligned under the circular aperture 50 in the upper plate.
  • the longitudinal wall 56 is a bearing surface for the automatic cap removal.
  • FIG 3 only a single set of apertures in plate 44 is illustrated although 50 such sets, in a 5 x 10 array are contemplated.
  • only a single aperture 54 is illustrated in plate 46 although a 5 x 10 array is contemplated.
  • the rack is positioned at a first station in the apparatus of the present invention.
  • the apertures 54 permit access to the cuvettes under rack 42.
  • cap removal means 60 are provided for automatically removing the cap 20 from the lower end of each column.
  • Figure 4 illustrates two positions of the cap removal means 60, an intermediate position illustrated by dashed lines and an active position illustrated by solid lines. It will be apparent that upper plate 44 has been omitted from the drawing in Figure 4.
  • the automatic cap removal means 60 is an elongated, thin, stainless steel spring strip extending generally vertically (or, more exactly, at 5.5° angle from the vertical) through the rectangular portions of the apertures 52, 54 in the upper and lower plates of the rack 42.
  • the elongated, thin, steel spring includes a fork portion 64 at the lower end, an apertured upper end 66 for attachment to an actuating mechanism 139, and a series of intermediate portions 68 and 70 therebetween, one of which intermediate portions bears against the bearing surface wall 56 as the cap removal means is moved vertically downward within the rack 42.
  • the cap removal means is attached to actuating mechanism 139 by screws (not shown) extending through the apertures in end 66.
  • the spring strip 60 engages the longitudinal wall 56 in the lower plate 46.
  • Means are provided for automating the column chromatography processing including such steps as applying hemolysate to the sample, agitating the column, running a buffer through the column, thereafter adding a sample to the column, adding a reagent to the column, etc.
  • the present invention includes certain features which are not found in the prior art, e.g. the provision of constant, low pressure for the chromatographic columns which are being processed. The pressure system will now be explained.
  • the pressure system includes a compressor 80 for providing constant air pressure to an input port 81 of a regulator 82.
  • the regulator 82 also includes an output port 83.
  • the regulator 82 includes two pressure relief bores 84, each of which is generally T-shaped in cross section, and air from the compressor 80 flows through the input port 81, through the main conduit 86 and through the output port 83 of the regulator.
  • the two relief bores 84 are provided to permit operation of the regulator at two different constant pressures.
  • each relief bore is provided with a projectile shape plunger 88, the plunger in one relief bore being of a different weight than the plunger in the other relief bore.
  • each relief bore 84 may be selectively closed at the exterior surface thereof such that only one relief bore will be in use at any given time.
  • Figure 7 illustrates the orientation of the regulator 82 when it is mounted on a chassis 85 during use.
  • relief bores 84 are positioned at an angle relative to the vertical axis. In operation, with the plungers mounted within the respective relief bores and with one of the relief bores open and the other closed, if the air pressure through the conduit exceeds a threshold as determined by the weight of the plunger associated with the open relief bore, the air will move the respective plunger upward opening a fluid flow path through the relief bore thus providing for a bleed of air pressure. When sufficient air pressure bleeds out through the relief bore, the plunger drops back to seal the relief bore from the main conduit. Selector valves (not illustrated) permit pressure relief bores 82 to be selectively sealed from main conduit 86. Positioning the plungers in bores 84 at an angle to the vertical facilitates movement of the plungers.
  • a low but constant air pressure is maintained at the output port 83.
  • the pressure that is selected should be high enough to increase the flow rate through the chromatographic columns but not high enough to compress the resin beds of the columns or to allow the fluid in the beds to be expelled.
  • the optimum pressure will depend on the properties of the columns and the resin matrixes therein. For example, a pressure of about 7473 pa (three inches of water) has been found to be appropriate for columns with a cellulose resin available from Whatman Incorporated, while a pressure of about 19927 Pa (eight inches of water) has been found to be appropriate for columns with "Emberlite” CG50 resin, available from Rohm & Haas ("Emberlite” is a Trade Mark).
  • the weights of the two plungers may be selected such that one plunger is sufficiently light so as to permit a constant air pressure equivalent to 7437 Pa (three inches of water) for example, and the second plunger is slightly heavier, thus permitting a constant air flow pressure at 19927 Pa (eight inches of water) for example.
  • the low pressure employed is not limited to the range of 7437 - 19927 Pa (three - eight inches of water). Less than 7437 Pa (three inches) or more than 19927 Pa (eight inches) may be utilized as the constant low pressure, depending on the particular chromatographic columns that are used.
  • regulator 82 can be simplified if a high quality piston compressor is used for compressor 80. Screw-adjustable needle valves (not shown) can then be used in lieu of plungers 88 to provide air at a fairly constant low pressure to the columns.
  • each manifold 94 is connected to a pressure tip system of the present invention for providing the desired pressure to each of the chromatographic columns while, at the same time, preventing leakage of air if less than a full array of columns is being processed by the system.
  • the pressure tip system as illustrated in Figure 8 in the absence of a chromatographic column, includes an upper block or manifold 94 having a conduit 96 therethrough in fluid communication through tube 93 with the output 83 of the pressure regulator.
  • Mounted partially within the block 94 is an elongated pressure cylinder 98, of generally circular cross section, having three reduced diameter circumferential recesses machined therein.
  • cylinder 98 has an upper grove or recess 100 machined therein, the upper groove positioned inwardly of a flange 102.
  • An O-ring seal 104 is positioned within the groove 100.
  • a second groove 106 is provided intermediate the two ends of the cylinder 98, and an O-ring 108 is positioned in the second groove 106.
  • a third groove 110 is provided in the cylinder adjacent the second end and is spaced inwardly therefrom such that a lower flange 112 is provided at the second end of the cylinder 98, and a flexible, foam gasket 114 is provided and mounted in the groove 110, the foam gasket 114 being retained by the flange 112.
  • the cylinder 98 has a longitudinal bore 116 extending through the flange 112 and through the body of the cylinder, the bore 116 extending along the longitudinal center line of the cylinder of the upper groove 100.
  • a transverse bore 118 is provided generally perpendicular to the longitudinal bore 116 and intersecting the longitudinal bore 116 at the end thereof inwardly of the upper groove 100.
  • the longitudinal bore 118 is in fluid communication with a circular passageway 120 which is provided within the block 94.
  • the pressure tip system is positioned as illustrated in Figure 8 such that the weight of the pressure tip system pulls the cylinder vertically downwardly causing the O-ring 104 to seal the top of the passageway 120 from the conduit 96, thus preventing the air flow from entering the vertical passageway 120.
  • a spring (not illustrated) can also be used above flange 102 to urge pressure cylinder 98 downward.
  • O-ring 104 functions both as a seal and also as a retainer which engages the flange 102 and prevents the cylinder mechanism 98 from dropping downwardly out of the passageway 120 of the block 94.
  • the entire pressure system is movable such that cuvettes may be placed in the chassis, and chromatographic columns may be placed in frame 42 within the chassis. Thereafter, the pressure system is moved into position relative to the chromatographic columns and lowered into position such that for each chromatographic column mounted in the rack 42, the top end of the column 10 engages the underside of the foam gasket 114 and pushes upward on the foam gasket such that the foam gasket, while still mounted in the groove 110, moves the cylinder 98 upwardly until the O-ring 108 seals the vertical passageway 120 at the bottom of the block 94.
  • each column presses upwardly on its respective foam gasket 114 to permit air pressure to flow into the top of the chromatographic column whereas in each position within the array, which is characterized by the absence of a chromatographic column, the pressure system remains in the position of Figure 8, and no air enters the cylinder 98 associated therewith.
  • the apparatus of the present invention includes a chassis or frame 130.
  • the frame or rack 42 for the chromatographic columns is mounted within a housing 132 to the frame.
  • Figure 10 also illustrates the five manifolds 94 positioned above the rack 42, the five manifolds or blocks extending from the front to the rear of the housing 132.
  • the cuvettes are positioned below the housing 132 as will be described hereinafter.
  • the apparatus includes a control housing 133 with a control panel 135.
  • a printer is disposed in control housing 133 to print out test results
  • a sample rack is mounted on the front wall of housing 132 to hold small cups containing specimens that are to be transferred to the chromatographic columns.
  • a horizontal support block 134 is mounted for movement laterally, i.e., in the "X" direction. Thus, the block 134 moves left and right.
  • the needles and actuating mechanism move as a group in the "Y" direction, i.e., forwardly and rearwardly of the block 134. They also move in "Z" or vertical direction.
  • Syringe pumps 137 are mounted on housing 133 and connected via tubing, not illustrated in Figure 10, to two of the needles. The syringe pumps transfer the samples and various fluids known in the art to the chromatographic columns.
  • a tray 142 for supporting the cuvettes is slidably mounted under the housing 132 (see Figure 11).
  • Figure 11 illustrates, in perspective, the tray 142 for the cuvettes, the tray including a generally flat surface or floor 144 upon which the cuvettes are placed, the floor being provided with guide rails 146 on three sides thereof.
  • a handle 148 is provided on the tray for movement of the tray of cuvettes into and out of the apparatus of the present invention.
  • the tray of cuvettes has been removed from Figure 10 for the purposes of clarity and ease of illustration.
  • Figure 12 illustrates, in perspective form, a rear view portion of the apparatus of the present invention, including the movable pressure tip system for engagement with the chromatographic columns.
  • three of the manifolds of blocks 94 are visible, as is the upper plate 44 of the rack 42 with two chromatographic columns 10 in place, one in each of two rows.
  • part of an L-shaped link 152 (also see Figures 15 and 16) is visible. It is pivotably connected to a leg 150 which is attached to the manifolds 94. Four such legs 150 are provided to support the manifolds, and each is pivotably connected to a respective link 152.
  • the links 152 When the system is in the position illustrated in Figure 12, the links 152 are disposed in an upright position and the manifolds 94 are in their raised positions, offset from the columns 10. In this raised and offset position, the needles 136, 137, 138 can access the tops of each of the chromatographic columns so that resuspension, separation, regeneration, or other fluids may be introduced therein or so that resuspension or other operations can be conducted.
  • Figure 13 is a perspective illustration similar to Figure 12 except that the links 152 have been rotated and the manifolds are now in their lowered position.
  • the links 152 are rotated from their upright positions, there is a downward swinging movement of the manifolds 94 such that the manifolds 94 move above the columns 10 and the pressure tip system of Figures 8 and 9 makes contact with the tops of the columns.
  • Figure 14 illustrates an enlarged, partial front elevation view of the apparatus of the present invention with the door 153 of control housing 133 ( Figure 10) open.
  • a first group of mixing needles 154 is illustrated.
  • the cuvette is moved to the right in Figure 14 by a stepping motor and is held in position underneath the needles 154 such that the fluid within each cell may be thoroughly mixed.
  • the cuvette is then moved further to the right in Figure 14 to be scanned by an optical reader 156 (see Figure 17). After scanning by the optical reader 156, the cuvette advances further to the right under a second group of needles 158 which remove fluid from the cuvette cells.
  • cuvette cell 38d is larger than the other three cuvette cells. This is because in column chromatography, it is common to collect eluates and, in a separate container, dilute a second sample (e. g., of blood or other biological fluid) such that comparative optical density readings may be taken for providing a reference standard for the purpose of quantifying purified fractions thereof relative to the standard. This technique is, of course, well known.
  • Figure 15 illustrates, in diagrammatic form, linkage and a motor 160 for moving the manifold system to the raised position, in which the manifold system is retracted relative to the tops of the individual chromatographic columns such that reagents, and samples and the like may be introduced therein.
  • the L-shaped links 152 are in their upright position in Figure 15.
  • Figure 16 illustrates, diagrammatically, the linkage and motor system of Figure 15 in the engaged position, illustrating the 90° rotation of the aforementioned links 152. It should be noted that while Figures 12 and 13 provide a rear perspective illustration, Figures 15 and 16 provide a front elevation diagrammatic illustration.
  • the rack 42 (not shown in Fig.17) is attached to a frame 131 that is movably mounted within housing 132.
  • a motor 133 (indicated by dotted lines) is provided to shift frame 131 and thus rack 42 laterally so that each column can be positioned above different cells.
  • block 134 is illustrated as mounted to a stepping motor system 162 which moves the block 134 laterally through a drive belt 164.
  • the columns are processed from right to left and from front to back of the system illustrated in Figure 17.
  • the cuvettes are processed from left to right and from back to front.
  • a bar or fence 166 extends across the width of the housing 132, underneath the housing but above the tray 142, and both ends of the bar are connected to a drive mechanism 168. Advancing the drive mechanism 168 moves the bar 166 forwardly such that five cuvettes 24 (not shown in Fig.17), one from each row, move forwardly clear of the tray 142 and onto a drive mechanism 170.
  • Drive mechanism 170 incudes a pusher block 172 which advances the cuvettes sequentially underneath the mixer needles 154, through the optical reader 156, and thereafter underneath the evacuator needles 158, which are connected through a pump to a waste evacuation system.
  • the mixer needles 154 are cleaned in a wash tray 155 and the evacuator needles 158 are cleaned in a similar wash tray 157 (not shown in Figure 17).
  • Drive system 168 advances the bar 166 forward, yet another step, such that the next row of five cuvettes may be deposited onto the drive belt 170 and processed sequentially.
  • Figure 17 also illustrates a cuvette 24a dropping off the drive mechanism after the completion of mixing, reading and evacuation.
  • the technician attending the apparatus may remove all of the chromatographic columns 10 from the rack 44 and replace them with new ones in preparation for the next cycle of tests.
  • economic circumstances may make it preferable to regenerate the columns 10 that have just been used instead.
  • the column analyzer system is configured to permit regeneration without removing the columns 10 from the rack 42 if the columns are being regenerated for immediate re-use. Three regeneration techniques are particularly suitable.
  • the technician reloads tray 142 ( Figure 11) with cuvettes 24, and then reinserts the tray 142 in the opening 282 (see Figure 10) beneath housing 132.
  • the needles are then used to transfer a diluted acid to each of the columns 10, followed by water.
  • the tray 142 is removed and the cuvettes are emptied into a waste receptacle.
  • Fresh cuvettes that will be employed during the next testing run are loaded onto tray 142, which is then inserted into opening 282 before the next testing run is begun.
  • the columns 10 have an affinity-type chromatographic media and have just been used during tests in which the specimens were blood.
  • the chromatographic medium in the columns is contaminated with sorbitol, a type of sugar, which must be removed to restore the medium.
  • the sorbitol can be stripped away using five milliliters of a 0.1 molar concentration of hydrochloric acid, followed by 5 milliliters of water to flush out the acid.
  • Hydrochloric acid is recommended, although other acids such as sulfuric acid, nitric acid, or acetic acid may be used.
  • the molar concentration of the acid may range from about 0.5 to about 0.05, with 0.1 being recommended. Enough of the acid solution must be used in each column to remove the greatest possible deposit of sorbitol that might be encountered, and this must be followed by enough water to flush out the greatest acid residue that might remain.
  • the tray 142 is not used in the second of the regeneration techniques mentioned above. Instead, after tray 142 has been removed a modified tray 159 (see Figure 25) is inserted into opening 282 to collect the dilute acid and water which drips through the columns.
  • Tray 159 is open at its top, and includes four walls 161 and a bottom 163.
  • a pipe 165 is connected to bottom 163 at a drain opening (not illustrated) in bottom 163.
  • Bottom 163 is shaped to slope slightly toward the drain opening.
  • Rails 165 are attached to the two walls 161 at the sides of tray 159. The rails 165 slide on corresponding rails (not shown) in the chromatographic apparatus when tray 159 is inserted into opening 182. At the corners between wall 161, tray 159 is sealed with a silicon-based sealant.
  • pipe 165 is connected by tubing to a waste receptacle. After the regeneration procedure the dilute acid and water in the waste receptacle is emptied, and the modified tray is withdrawn from opening 282. A tray 142 of cuvettes can then be inserted to begin a new testing run.
  • a tray (not illustrated) corresponding to tray 159 is permanently mounted in the chromatographic apparatus, at a position below tray 142. The acid solution and water can then drip into it when tray 142 is removed.
  • stepping motor 176 (illustrated diagrammatically in Figure 17) is provided for driving a cam arrangement such that, at the completion of the chromatographic separation step, rotation of the motor causes raising and lowering the rack 42. This movement causes any drops at the bottom of the tips of the chromatographic columns 10 to drop into the respective cells of the cuvettes 24.
  • This drop removal feature will be described in more detail with reference to Figures 18 and 19.
  • FIG. 18 A top view of drop removal mechanism 200 by itself is shown in Figure 18, and Figure 19 illustrates a front view of mechanism 200 in its operative position beneath top plate 44 of rack 42.
  • Mechanism 200 includes a pair of rods 202 which are journaled for rotation beneath plate 44. Rods 202 extend parallel to manifolds 94 (see Figure 10). Rectangular plastic blocks 204 are attached in an eccentric manner to the rods 202. A block 204 is positioned adjacent each corner of plate 44. Crank members 206 are also attached to bars 202, preferably at a position behind plate 44. Each end of a link 208 is pivotably attached to a crank member 206. Link 208 and crank members 206 cause rods 202 to rotate in unison.
  • Drop removal mechanism 200 also includes a pin 210 affixed to one of the rods 202. Pin 210 is positioned for engagement by a cam 212 which is rotated by stepping motor 176.
  • Rack 42 normally rests on a support (not illustrated) but is mounted so that it can slide upward slightly from the support.
  • cam 212 undergoes a clockwise revolution (with respect to Figure 19)
  • it encounters pin 210 and causes rods 202 to rotate by about 90° before cam 212 separates from pin 210.
  • blocks 204 urge plate 44 and thus rack 42 upward about an eighth of an inch (2.54 cm) above the support.
  • Rack 42 drops back to the support when cam 212 disengages from pin 210. The resulting jar is sufficient to jiggle loose any drops suspended at the end of the columns 10 supported by the rack 42.
  • drop removal mechanism 200 improves the accuracy of the measurements made by the automatic column chromatography machine.
  • fluids are introduced to each column 10 in a sequence, and the eluates from the column are collected in different cells of the cuvette means 24 ( Figure 2).
  • Accuracy would suffer if even a small amount eluate intended for one cell were to contaminate the eluate collected in an adjacent cell.
  • motor cell 176 is actuated to rotate cam 212 by a revolution after each solution has been introduced to the column 10, and before the column is advanced to the next position over an adjacent cell. The result is that the last drop falls into the cell intended instead of the adjacent cell.
  • the three needles 136, 137, and 138 and the actuating mechanism 139 each move in the "Z" direction under influence of motors.
  • the needles 136, 137, and 138 provide for mixing or agitation of the resin in the columns as well as providing conduits for the addition of reagents and/or samples into the columns.
  • vertical movement of actuating mechanism 139 (also see Figure 4) provides for removal of the caps from the columns.
  • Actuating mechanism 139 functions to move spring 60 downwardly.
  • bellows-motor 180 illustrated in Figure 17 wherein four bellow systems are shown, each associated with one of the needles 154 and each attached to a motor 182.
  • Motor 182 rotates, and an internal threaded nut system converts the rotation motion of the motor 182 into linear motion of the bellows 180 which, in turn, moves the fluid in the needles 154 vertically for mixing the liquid in the cuvette cells prior to the liquid passing through the optical reader 156.
  • the bellows-motor arrangement illustrated with respect to the needles or mixer unit 154 may be replicated for movement of the needles 136-139 as they provide controlled, bi-directional movement in small increments.
  • Figure 20 illustrates an alternate embodiment for the pressure tip units, and a modified chromatographic column with which it is used.
  • the arrangement shown in Figure 20 avoids the need to manually unscrew covers 12 (Figure 1) when the columns are loaded into the rack 42.
  • an improved chromatographic column 214 in accordance with the present invention includes a polypropylene shell which defines a reservoir portion 216, a barrel portion 218 (shown broken away to reduce its length in the drawing), and a tip portion 220.
  • a fluid-pervious disk 222 lodged inside the shell supports a chromatographic medium 224 within barrel portion 218.
  • the medium may be, for example, ion exchange resin particles, affinity resin particles, size-exclusion resins, or matrix-type media such as cellulose, agarose, or silica gel.
  • a removable cap 226 closes the lower end of tip portion 216.
  • a foil seal member 228 closes the top end of reservoir portion 216.
  • seal member 228 is fused to the shell using heat (alternatively, adhesive bonding or ultrasonic bonding can be employed).
  • Member 228 includes an adhesion layer 230 of polyethylene which readily fuses with the plastic of the shell. Polypropylene could also be used in layer 230.
  • Layer 230 is bonded to an intermediate layer 232, such as polypropylene.
  • Polyethylene could also be used in layer 232.
  • An aluminum layer 234 is bonded to 232.
  • Layer 232 serves as a moisture barrier. The thickness of layers 230-234 is exaggerated in Figure 20 for ease of illustration.
  • Layers 230 and 232 are preferably 2.54 x 10 ⁇ 3 cm (a thousandth or so of an inch) thick each.
  • Layer 234 is less than about 7.62 x 10 ⁇ 3 cm (three thousandths of an inch) thick, and preferably about 2.54 to 5.08 x 10 ⁇ 3 cm (one to two thousandths of an inch) thick.
  • the pressure tip unit that cooperates with column 214 includes a pressure cylinder 236 having three reduced-diameter circumferential recesses machined therein. Cylinder 236 extends movably through a bore in manifold 94. O-rings 104 and 108 are lodged in two of the recesses, and a foam gasket 114 is lodged in the third. An axial bore 238 communicates with a bore 240 across the diameter of cylinder 236. A seal-punching head 242 is provided at the bottom of cylinder 236.
  • head 242 is initially machined to be conical, with a 90° apex angle (that is, the surface has a 45° angle with respect to the longitudinal axis of cylinder 236). Then one side of head 242 is ground to provide a flat region 244. This leaves a cutting edge 246 (see Figure 22) along one rim of the bottom opening of bore 238.
  • the aluminum layer 230 being relatively thick, not only provides a secure closure during transportation and handling of the columns 214, it also prevents the ruptured seal member 228 from springing back after the pressure cylinder 236 has been withdrawn. That is, the aluminum remains permanently deformed and prevents the hole formed by head 242 from closing up.
  • Pressure cylinder 236 can of course replace pressure cylinder 98.
  • An axial blind bore (not shown) can be drilled from the top to hold a spring (not shown) as an aid to closing pressure cylinder 98.
  • FIGS 21A-21C illustrate a cap removal means 248 that can be used in lieu of the cap removal means 60 shown in Figures 4 and 5A-5C.
  • Cap removal means 248 includes a fork portion 250, intermediate portions 252, 254, 256, and 258, and an end portion 260.
  • Cap removal means 248 is made from a stainless steel strip and cooperates with bearing surface 256 ( Figures 3 and 4) in the manner previously discussed with respect to cap removal means 60. However, while cap removal means 60 is flexed slightly and acts as a spring during operation, cap removal means 248 is substantially inflexible.
  • Fork portion 250 is preferably 0.86 cm (0.34 inches) long and has a generally v-shaped slot with a rounded bottom.
  • Intermediate portion 252 is preferably 1.02 cm (0.40 inches) long and forms an angle of 120° with fork portion 250.
  • Intermediate portion 254 is preferably 0.99 cm (0.39 inches) long and forms an angle of 135° with intermediate portion 252.
  • Intermediate portion 256 is preferably 1.68 cm (0.66 inches) long, and forms an angle of 132° with intermediate portion 254.
  • Intermediate portion 258 is preferably 0.94 cm (0.37 inches) long and forms an angle of 123° with intermediate portion 256.
  • End portion 260 is preferably 2.95 cm (1.16 inches) and forms an angle of 120° with intermediate portion 158.
  • Figure 24 shows cap removal means 248 attached to an actuating mechanism 139′ having a flattened lower end 262.
  • Pegs 264 are attached to lower end 262 and extend through the smaller openings in end portion 260 shown in Figure 21C.
  • a screw 266 extends through the central opening, with the head of screw 266 being spaced apart from the surface of cap removal means 248.
  • a coil spring 268 is disposed around the shaft of screw 266 beneath the head of the screw, and normally biasses portion 260 against flattened lower end 262.
  • cap removal means 248 is pivoted about its upper end 272, and fork portion 250 swings in the direction of arrow 274 toward the tip portion 18 (see Figures 1 and 4) of a column 10.
  • portion 256 slides against bearing surface 56 and the cap 20 at the tip of the column is dislodged.
  • spring 268 urges cap removal means 248 back to its original position with respect to actuating mechanism 139′.
  • pegs 264 serve to keep cap removal means 248 aligned, and that pegs 264 are not affixed to cap removal means 248 but are, instead, slightly movable with respect to it.
  • Spring 268 is shaped like a truncated cone, when seen from the side. Because of this, spring 268 can be flattened so that its coils are nested inside one another. Thus spring 268 can undergo considerably more compression than could a cylindrical spring.
  • Spring 268 is preferably made of stainless steel, with a copper coating to prevent the stainless steel from gauling.
  • actuating mechanism 139′ is shown with a rack of teeth 276 for engagement with a gear (not shown) rotated by a motor (not shown) in support block 134 (see Figures 10 and 17) to raise or lower actuating mechanism 139′.
  • Actuating mechanism 139 may similarly be provided with a rack of teeth.
  • Figure 23 shows a modification of Figure 14 which avoids the need for the bellows 180 and motors 182 shown in Figure 17.
  • a plate 262 is mounted on a wall 263 so as to be movable up and down. Wall 263 is movable forward and backward.
  • a paddle assembly 264 with three paddles is mounted on plate 262. The paddles are lowered into cells 38b, 38c, and 38d of cuvette 24 and then moved forward and backward to mix the contents thereof.
  • the paddle for cell 38d is larger than the rest since cell 38d itself is larger than the other cells.
  • a fourth paddle is not needed since the content of cell 38a is not normally read-- it contains the cap 20 and a buffer solution that was drained from the column before use.
  • the needles 158 for evacuating the cuvettes are still used. However, the flexible hoses shown leading to the needles 158 in Figure 14 are diverted behind plate 276 in the embodiment of Figure 23.
  • the foregoing is a complete description of a preferred embodiment of the present invention.
  • the invention automates those steps normally performed by a technician in a manual pipetting operation, and the individual steps, per se, are conventional.

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EP19920306568 1991-07-22 1992-07-17 Column analyser system and chromatographic column Withdrawn EP0527562A3 (en)

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US73371491A 1991-07-22 1991-07-22
US733714 1991-07-22
US779186 1991-10-22
US07/779,186 US5228988A (en) 1989-10-27 1991-10-22 Column analyzer system and improved chromatograph column for use in the system

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997044670A1 (de) * 1996-05-21 1997-11-27 Abion Beteiligungs- Und Verwaltungs-Verwaltungs-Gesellschaft Mbh Pipettierautomat
FR2760843A1 (fr) * 1997-03-14 1998-09-18 Gilson Med Electr Appareil de preparation d'echantillons avec ascenseur
EP2103680A1 (de) * 2007-01-19 2009-09-23 Universal Bio Research Co., Ltd. Pipettenchip mit darin eingeschlossener stütze oder flüssigkeit, vorrichtung zur bearbeitung eines pipettenchips mit darin eingeschlossener stütze oder flüssigkeit und verfahren zur bearbeitung eines pipettenchips mit darin eingeschlossener stütze oder flüssigkeit
WO2009120516A1 (en) * 2008-03-25 2009-10-01 Ortho-Clinical Diagnostics, Inc. Immunodiagnostic test element having weakened foil layer
WO2014096136A2 (en) * 2012-12-19 2014-06-26 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Reaction vessel for sample preparation

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5554291A (en) * 1992-10-23 1996-09-10 Scanzillo; Joseph G. Methods and apparatus for biodegradation of polluted fluids
JP3985872B2 (ja) * 1995-07-31 2007-10-03 プレシジョン・システム・サイエンス株式会社 容器
WO1998001760A2 (en) * 1996-07-05 1998-01-15 Beckman Coulter, Inc. Automated sample processing system
US5800784A (en) 1996-07-09 1998-09-01 Horn; Marcus J. Chemical sample treatment system and cassette, and methods for effecting multistep treatment process
GB9711941D0 (en) * 1997-06-09 1997-08-06 Acgt Medico Inc Detection of pathogens
US6090278A (en) * 1998-08-20 2000-07-18 Dyax Corporation Apparatus and method for sealing a plurality of chromatography columns
EP1889526B1 (de) * 2005-05-23 2010-01-20 Agilent Technologies, Inc. Trägerplatte einer einrichtung
US10113996B2 (en) * 2014-05-14 2018-10-30 Ge Healthcare Bio-Sciences Ab Chromatography lab system for analyzing samples including a cooling compartment with an identifying device that identifies a fraction collector device
CN108027280B (zh) 2015-06-26 2021-07-06 雅培实验室 用于使得反应容器在诊断分析仪中从处理轨道运动至旋转装置的反应容器运动部件
WO2019194935A1 (en) * 2018-04-05 2019-10-10 Emd Millipore Corporation Chromatography media handling and packing equipment

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0409606A2 (de) * 1989-07-19 1991-01-23 Tosoh Corporation Automatisches Analysiergerät und Verfahren zur Anwendung desselben
EP0425297A2 (de) * 1989-10-27 1991-05-02 Helena Laboratories Corporation Säulenanalysensystem
WO1991008464A1 (en) * 1989-12-01 1991-06-13 Akzo N.V. Sample handling system for an optical monitoring system

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1598212B2 (de) * 1964-05-26 1971-03-04 Ceskoslovenska akademie ved , Prag Verfahren und einrichtung zum herstellen von dosierten gemischen
SE326056B (de) * 1966-01-07 1970-07-13 Ceskoslovenska Akademie Ved
US3926809A (en) * 1973-10-10 1975-12-16 Roosevelt J Jones Multi-column fractionator
JPS5630500B2 (de) * 1974-02-27 1981-07-15
US3922223A (en) * 1974-03-25 1975-11-25 Us Navy Multiple chromatographic column system
DE2418509C3 (de) * 1974-04-17 1978-04-27 Sartorius-Membranfilter Gmbh, 3400 Goettingen Vorrichtung zur halbautomatischen gleichzeitigen säulenchromatographischen Auftrennung einer Vielzahl von Probenlösungen
DE2545997C3 (de) * 1975-10-14 1978-09-07 Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V., 3400 Goettingen Vorrichtung für die Vielfach-Säulenchromatographie
US4341635A (en) * 1980-12-16 1982-07-27 Helena Laboratories Corporation Microchromatographic column and method
US4604198A (en) * 1984-05-18 1986-08-05 Amf Inc. Multicartridge chromatography cartridge housing
FR2572180B1 (fr) * 1984-10-24 1987-03-20 Eric Marteau D Autry Procede et appareil de reparation d'echantillons a des fins d'analyse
CA1325980C (en) * 1987-04-22 1994-01-11 Sho Kikyotani Apparatus for the treatment of biological samples and treatment methods using the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0409606A2 (de) * 1989-07-19 1991-01-23 Tosoh Corporation Automatisches Analysiergerät und Verfahren zur Anwendung desselben
EP0425297A2 (de) * 1989-10-27 1991-05-02 Helena Laboratories Corporation Säulenanalysensystem
WO1991008464A1 (en) * 1989-12-01 1991-06-13 Akzo N.V. Sample handling system for an optical monitoring system

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997044670A1 (de) * 1996-05-21 1997-11-27 Abion Beteiligungs- Und Verwaltungs-Verwaltungs-Gesellschaft Mbh Pipettierautomat
FR2760843A1 (fr) * 1997-03-14 1998-09-18 Gilson Med Electr Appareil de preparation d'echantillons avec ascenseur
WO1998041875A1 (fr) * 1997-03-14 1998-09-24 Gilson S.A. Appareil de preparation d'echantillons avec ascenseur
US6261520B1 (en) * 1997-03-14 2001-07-17 Gilson, S.A. Apparatus for preparing samples with slider box
EP2103680A4 (de) * 2007-01-19 2013-01-02 Universal Bio Research Co Ltd Pipettenchip mit darin eingeschlossener stütze oder flüssigkeit, vorrichtung zur bearbeitung eines pipettenchips mit darin eingeschlossener stütze oder flüssigkeit und verfahren zur bearbeitung eines pipettenchips mit darin eingeschlossener stütze oder flüssigkeit
EP2103680A1 (de) * 2007-01-19 2009-09-23 Universal Bio Research Co., Ltd. Pipettenchip mit darin eingeschlossener stütze oder flüssigkeit, vorrichtung zur bearbeitung eines pipettenchips mit darin eingeschlossener stütze oder flüssigkeit und verfahren zur bearbeitung eines pipettenchips mit darin eingeschlossener stütze oder flüssigkeit
WO2009120516A1 (en) * 2008-03-25 2009-10-01 Ortho-Clinical Diagnostics, Inc. Immunodiagnostic test element having weakened foil layer
US9562921B2 (en) 2008-03-25 2017-02-07 Ortho-Clinical Diagnostics, Inc. Immunodiagnostic test element having weakened foil layer
US10018645B2 (en) 2008-03-25 2018-07-10 Ortho-Clinical Diagnostics, Inc. Immunodiagnostic test element having weakened foil layer
WO2014096136A2 (en) * 2012-12-19 2014-06-26 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Reaction vessel for sample preparation
WO2014096136A3 (en) * 2012-12-19 2014-09-04 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Reaction vessel for sample preparation
CN104994956A (zh) * 2012-12-19 2015-10-21 马克斯·普朗克科学促进协会 用于样品制备的反应容器
JP2016503163A (ja) * 2012-12-19 2016-02-01 マックス−プランク−ゲゼルシャフト・ツア・フェルデルング・デア・ヴィッセンシャフテン・エー・ファオ 試料調製のための反応槽
US9791355B2 (en) 2012-12-19 2017-10-17 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Reaction vessel for sample preparation
AU2013360712B2 (en) * 2012-12-19 2018-06-28 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Reaction vessel for sample preparation

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JPH05196611A (ja) 1993-08-06
CA2074245A1 (en) 1993-01-23
EP0527562A3 (en) 1993-06-23
US5228988A (en) 1993-07-20

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